Popular Drug May Damage Brain

By SANDRA BLAKESLEE

Published: August 15, 1995

IN experiments on animals, a popular street drug called Ecstasy caused the brain to form abnormal connections that could lead to problems like chronic depression, scientists have reported.

The changes, which affect nerve cells throughout the brain, have been shown to occur in monkeys given recreational doses of the drug. Thus the finding is likely to apply to humans as well, said Dr. George Ricaurte, an assistant professor of neurology at the Johns Hopkins University School of Medicine in Baltimore, who carried out the research.

Dr. Lewis Seiden, a neuropharmacologist at the University of Chicago, said, "This is an important basic research discovery with implications for people who take MDMA," or Ecstasy. The drug, a methamphetamine derivative, may have long-term, harmful effects on appetite, sleep, mood, impulsiveness and other mental functions, he said. Similar problems may occur in people taking a chemically related diet pill, fenfluramine, which is popular in Europe.

The extent of the damage probably varies with dosage, Dr. Ricaurte said. People who take Ecstasy three or four times a year might not notice any changes in their behavior or thinking. But those who take large amounts -- like seven or eight doses a night during the dance parties called raves -- could be inviting more serious problems.

Dr. Ricaurte's study was published in the August issue of The Journal of Neuroscience and was supported by the National Institute on Drug Abuse.

Ecstasy is popular on campuses in the United States, Dr. Ricaurte said. In Britain, where raves are popular, it is the second most popular street drug, after marijuana.

After taking Ecstasy, people report an extraordinary loss of inhibitions and feel love toward their fellow human beings, Dr. Ricaurte said. Ecstasy produces its effects for four to six hours, he said, yet no one knows how the drug works.

It is known, however, that Ecstasy perturbs one of the brain's major chemical systems for transmitting information. The chemical serotonin is released from a bundle of nerve cells in the brain stem. These cells make dense, threadlike connections, called axons, to other nerve cells all over the brain and into the spinal cord. The axons, when electrically activated, squirt serotonin onto cells in the cortex, amygdala, hypothalamus and midbrain regions.

Previous research showed that Ecstasy destroys serotonin-carrying axons, Dr. Ricaurte said. The drug "literally prunes the axon projections," he said, while leaving the cell bodies alone. Then, in ways that are not yet understood, the axons tend to regenerate and make new connections in the brain.

The new research took a closer look at this process in rats and monkeys. Animals were given recreational doses of Ecstasy -- the amounts taken by many young people -- and their brains were examined 12 to 18 months later.

In rats, new axons grew and made normal-looking connections all over the brain, Dr. Ricaurte said. But in squirrel monkeys, he said, the axon regrowth "was markedly abnormal." Connections to nearby targets like the amygdala and hypothalamus -- circuits that help control emotion and hormone balance -- were overabundant. And reconnections to the higher cortex were absent.

It seems that the shorter axonal projections recover but the longer ones do not, Dr. Ricaurte said.

Serotonin helps regulate mood, appetite and cognition, Dr. Ricaurte said. People taking high doses of Ecstasy could suffer permanent damage to their serotonin systems, he said, which could lead to chronic mood, memory and sleep problems.

The appetite suppressant fenfluramine, sold under the trade name Pondimin, produces the same neurotoxicity as Ecstasy in mice, rats and monkeys, Dr. Ricaurte said. The worry is that people take diet pills for long periods. "It may well be that the doses used in humans could be without neurotoxic effects, but we should look," he said.

A Federal study last year found no evidence that fenfluramine caused permanent brain damage.